A 25-year-old African man presents with episodic hemolytic anemia precipitated by antimalarials. His G6PD level drawn during an acute episode is normal. The most appropriate next diagnostic step is:

• A Osmotic fragility test to confirm hereditary spherocytosis as co-diagnosis
• B Direct antiglobulin (Coombs) test to exclude autoimmune hemolysis
• C Heinz body preparation to confirm oxidative hemolysis without measuring enzyme activity
• D Repeat G6PD level 2–3 months after episode resolution, when reticulocytes have matured to erythrocytes ✓

Explanation

G6PD-deficient young erythrocytes and reticulocytes have higher enzyme activity than mature red cells due to enzyme decay over RBC lifespan. During acute hemolytic episodes, older G6PD-deficient cells are selectively destroyed, leaving a reticulocyte-rich population with relatively higher G6PD activity — thus a falsely normal result. G6PD should be measured 2–3 months after resolution when a steady-state erythrocyte population is present. Osmotic fragility tests hereditary spherocytosis. DAT evaluates autoimmune hemolysis. Heinz bodies confirm oxidative damage but do not quantify G6PD activity.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.